Clinical and immunohistochemical correlates of goitre versus hypoxia-inducible factors: an inferential hospital-based case-control study from Iraq
Paper Details
Clinical and immunohistochemical correlates of goitre versus hypoxia-inducible factors: an inferential hospital-based case-control study from Iraq
Abstract
Goitre, an abnormal enlargement of the thyroid gland, represents one of the most common endocrine disorders encountered in Iraqi patients. Several pathologic conditions, including thyroid malignancies, are correlated with the expression of hypoxia-inducible factors. Those are transcription factors that become activated in response to hypoxia. Our study will attempt to explore those factors in patients with goitre. The study is a hospital-based case-control in design. Individuals were allocated into cases (n=43) of individuals underwent a thyroidectomy procedures for goitre, and controls (n=25) who has conducted a total laryngectomy procedure for conditions unrelated to the thyroid gland. Histological samples were collected and examined via immunohistochemistry for hypoxia-inducible factors specifically HIF-1 and HIF-2. These were quantified and statistically tested with other parameters including age, gender, and the existence of clinical toxicity. Patients with goitre had significantly higher levels of HIF-1 and HIF-2 compared to controls (p-value<0.001). Clinically-toxic patients had substantially higher levels of both HIF-1 and HIF-2 than non-toxic patients (p=0.019, p=0.072). Patients, especially clinically-toxic ones, had notably more elevated levels of HIF-1 and especially when they grew older compared to non-toxic patients. Besides, the levels of HIFs appear to be rising in positive correlation with each other. Although our study has a high level-of-evidence, it may have some limitations. Nevertheless, it represents the first retrospective case-control study from Iraq in connection with the investigation of hypoxia as a cellular-biochemical event in patients from the Iraqi population.
Abd‑Aziz N, Stanbridge EJ, Shafee N. 2015. Bortezomib attenuates HIF-1-but not HIF-2-mediated transcriptional activation. Oncology letters 2192-6.
Al-Rrawak K, Al-Sarraf SA, Sulaiman TI. 2009. Changing Patterns of Thyroid Pathology and Trends of Surgical Treatment. Journal of the Faculty of Medicine 51, 12-6.
Bersten DC, Sullivan AE, Peet DJ, Whitelaw ML. 2013. bHLH–PAS proteins in cancer. Nature Reviews Cancer 13, 827.
Brahimi-Horn MC, Chiche J, Pouysségur J. 2007. Hypoxia and cancer. Journal of molecular medicine 85,1301-7.
Burrows N, Resch J, Cowen R L, von Wasielewski R, Hoang-Vu C, West CM, Williams KJ, Brabant G. 2010. Expression of hypoxia-inducible factor 1α in thyroid carcinomas. Endocrine-Related Cancer 17, 61-72.
Castro MR, Gharib H. 2005. Continuing controversies in the management of thyroid nodules. Annals of internal medicine 142, 926-31.
Centre for Evidence-Based Medicine (CEBM, University of Oxford). 2017. OCEBM Levels of Evidence. www.cebm.net/2016/05/ocebm-levels-of-evidence
Eales KL, Hollinshead KE, Tennant DA. 2016. Hypoxia and metabolic adaptation of cancer cells. Oncogenesis 5, e190.
EB Rankin and AJ Giaccia. 2008. The role of hypoxia-inducible factors in tumorigenesis. Cell Death Differ 15, 678-685.
Gandolfi PP, Frisina A, Raffa M. 2004. The incidence of thyroid carcinoma in multinodular goiter: retrospective analysis. Acta Bio Medica Atenei Parmensis 75,114-7.
Greenhalgh T, Howick J, Maskrey N. 2014. Evidence based medicine: a movement in crisis?. Bmj 348, g3725.
Ke Q, Costa M. 2006. Hypoxia-inducible factor-1 (HIF-1). Molecular pharmacology 70,1469-80.
Koh MY, Lemos R, Liu XP, Powis G. 2011. The hypoxia associated factor (HAF) switches cells from HIF-1α to HIF-2α dependent signaling promoting stem cell characteristics, aggressive tumor growth and invasion. Cancer research, canres 4142.
Liu R, Xing M. 2016. TERT promoter mutations in thyroid cancer. Endocrine-related cancer: ERC-15.
Loboda A, Jozkowicz A, Dulak J. 2012. HIF-1 versus HIF-2—is one more important than the other?. Vascular pharmacology 56, 245-51.
Luna GL. 1968. Manual of histological staining of Armed Forces Institute of Pathology. 3rd edition. McGraw-Hill. USA. P-18.
Mahdi QA, Ahmed BS, Kadhim MA. 2010. The frequency of thyroid carcinoma in patients with solitary and multiple nodules utilizing ultrasound guided fine needle aspiration cytology (FNAC): A prospective study (Thyroid carcinoma and U/S guided FNA). Journal of the Faculty of Medicine 52,136-40.
Majmundar AJ, Wong WJ, Simon MC. 2010. Hypoxia-inducible factors and the response to hypoxic stress. Molecular cell 40, 294-309.
Mandel SJ. 2004. A 64-year-old woman with a thyroid nodule. Jama 1, 2632-42.
Munro BH. 1971. Manual of Histologic Staining Methods of the Armed Forces Institute of Pathology. Pathology 3, 249.
Påhlman S, Lund LR, Jögi A. 2015. Differential HIF-1α and HIF-2α expression in mammary epithelial cells during fat pad invasion, lactation, and involution. PLoS One 10, e0125771.
Smith TG, Robbins PA, Ratcliffe PJ. 2008. The human side of hypoxia‐inducible factor. British journal of haematology 141, 325-34.
Toschi A, Lee E, Gadir N, Ohh M, Foster DA. 2009. Differential dependence of hypoxia-inducible factors 1α and 2α on mTORC1 and mTORC2. Journal of Biological Chemistry 283, 34495-9.
Vooijs MA, Gort EH, Groot AJ, der Wall EV, van Diest PJ. 2008. Hypoxic regulation of metastasis via hypoxia-inducible factors. Current molecular medicine 8, 60-7.
Wang GL, Semenza GL. 1995. Purification and characterization of hypoxia-inducible factor 1. Journal of Biological Chemistry 27, 1230-7.
Zeng X, Zhang Y, Kwong JS, Zhang C, Li S, Sun F, Niu Y, Du L. 2015. The methodological quality assessment tools for preclinical and clinical studies, systematic review and meta‐analysis, and clinical practice guideline: a systematic review. Journal of evidence-based medicine 8, 2-10.
Zhao W, Han C, Shi X, Xiong C, Sun J, Shan Z, Teng W. 2014. Prevalence of goiter and thyroid nodules before and after implementation of the universal salt iodization program in mainland China from 1985 to 2014: a systematic review and meta-analysis. PloS one 9, e109549.
Mohammed H. Assi, Samia A. Eleiwe, Basem Sh. Ahmed, Ahmed Al-Imam, 2018. Clinical and immunohistochemical correlates of goitre versus hypoxia-inducible factors: an inferential hospital-based case-control study from Iraq. Int. J. Biosci., 13(4), 387-395.
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